Electron microscopy is a technique of fundamental importance in molecular and cell biology. Most of what we know about cell ultrastructure was learned from electron microscopy. Recently, several advancements have made possible he use of electron microscopy to obtain insight which go beyond descriptive information and the electron microscope has become a powerful tool to study molecular mechanisms. In large part, these developments reflect the advent of highly sensitive immunocythochemical techniques, of genetic methods to disrupt the function of individual proteins, and of cell free systems which make possible the analysis of isolated organelles or macromolecular complex. Furthermore, the advancements in cryoelectron microscopy are narrowing the gap between classical cell biology and structural biology. This application proposes the purchase of new transmission electron microscope (Philips CM120 BioTwin) and supporting equipment digital imaging. This instrumentation will be housed in the electron microscopy unit of the Center for Cell Imaging at the Yale School of Medicine. This is a shared facility, which is managed by the Department of Cell biology, but is subsidized by the School. It is used primarily by faculty from the Department of Cell Biology and other Departments whose research focuses on molecular and cell biology. The instrument will replace a Jeol 100cX which has been recently taken out of service The Yale Electron Microscopy Core Facility has traditionally been among the leaders in the application of electron microscopy to biology and medicine. While this continues to be the case, progress is now being hampered by microscope availability and by the outmoded instrumentation present in the facility. There have been major advances in electron microscope design and image digitalization and the facility is in urgent need of a state-of-the-art microscope. The productivity of Yale Cell Biology is crucially dependent on the availability of such an instrument.